A multi-center study of the Electroretinogram (ERG) in central retinal vein occlusion (CRVO) has been completed as an ancillary study to the central vein occlusion study (CVOS). The ERG study was designed to answer the primary question of whether an ERG obtained acutely following CRVO can be used to predict eyes at high risk to develop iris neovascularization (NVI). To this end, baseline ERGs from 412 CVOS patients at 8 centers have been obtained, graded and sent ot the CVOS data coordinating center. ERGs were also recorded at 4 month and 12 month visits a in 82% of these patients. Endpoint ERGs, recorded following the development of NVI, were recorded from 42 patients. The purpose of this proposal is to provide a mens for analysis of longitudinal changes in the ERG in relation to ophthalmologic, demographic and outcome measures obtained as part of the CVOS. Specific analyses proposed are: (1) To relate changes in ERG parameters known to be most sensitive to CRVO (logK, flicker phase, b/a amplitude ratio) to fundus photograph/fluorescein angiogram changes to better understand the natural course of CRVO. (2) To assess the clinical significance of outer retinal dysfunction as measured by changes in the ERG a-wave. (3) To evaluate changes in oscillatory potentials of the ERG, a measure known to be sensitive to other forms of retinal ischemia, and to assess their utility as predictors of final visual outcome. (4) To determine whether the ERG shows evidence of severe retinal ischemia as the pathophysiologic mechanism in all eyes developing NVI. (5) To determine whether eyes with hyper-responsive ERGs have a more likely to occur in patients with systemic disease and whether these abnormalities have any clinical significance. (6) To determine whether ERG abnormalities in the fellow eye are more likely to occur in patients with systemic disease and whether these abnormalities have any clinical significance. The CVOS-ERG data set is unique for its large size, degree of standardization of collection and grading protocols, and the availability of well documented clinical, photographic, and angiographic data. Analysis of longitudinal data will provide useful information regarding the pathophysiology and natural history of CRVO and may also provide evidence clinically significant changes in the ERG with therapeutic implications. GRANT-R01EY10826 When neurons respond to stimuli is at least as important as how much they respond. However, response timing has been largely neglected by visual neuroscientists. Motion processing is a key problem for the brain, and depends on timing information. Recent work has suggested that the cat visual system processes motion by creating a novel cell type in the lateral geniculate nucleus, lagged cells. Lagged cells differ from nonlagged cells by the timing of their responses. Lagged and nonlagged cells project to visual cortex, where the timing difference between them may be used to create direction-selective responses. Direction-selective cells appear to be a key substrate in motion in processing. For instance, raising cats in an environment illuminated only b a strobe light causes a specific loss of direction-selective cells, and causes a specific behavioral deficit in motion processing. The studies that have generated the results stated above relied on testing responses of adult cats. Strobe-rearing is a manipulation performed during a critical period early in a kitten's life, however. Young kittens appear to have many direction-selective cortical cells, but these cells differ in response timing from those seen in adults. Can we observe the formation of mature direction-selective cells in kitten visual cortex, and does this maturation correspond to what one would expect from the development of lagged and nonlagged cells in the lateral geniculate nucleus? Furthermore, can we follow the destruction of direction selectivity induced by strobe- rearing, and see whether this destruction comes about because of effects on the lagged and nonlagged inputs to cortex? These questions will be addressed by a study of the postnatal development of response timing in the lateral geniculate nucleus and visual cortex of cats. The goal is to determine when lagged and nonlagged cells arise as distinct cell groups, and more generally how geniculate response timing matures. These results will be compared to a parallel study of the development of cortical response timing. The details of the disruption of this normal development by strobe-rearing will be examined by recording from kittens with brief experience in the strobe environment. This work will help to show how the visual system deals with time , a well as how thalamic inputs influence cortical cells. In the long term, these results could suggest how the brain develops strategies for temporal processing, and this would have major implications for both basic and clinical research, for instance in treatment of learning disabilities.